TY - JOUR
T1 - Dissociation in Pharmacokinetic Attenuation Between Central Dopamine D2 Receptor Occupancy and Peripheral Blood Concentration of Antipsychotics
T2 - A Systematic Review
AU - Kurose, Shin
AU - Mimura, Yu
AU - Uchida, Hiroyuki
AU - Takahata, Keisuke
AU - Kim, Euitae
AU - Suzuki, Takefumi
AU - Mimura, Masaru
AU - Takeuchi, Hiroyoshi
N1 - Publisher Copyright:
© Copyright 2020 Physicians Postgraduate Press, Inc.
Copyright:
This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine
PY - 2020/7/28
Y1 - 2020/7/28
N2 - OBJECTIVE: The objective of this study was to examine the extent of possible dissociation in pharmacokinetic decay between central dopamine D₂ receptor occupancy with antipsychotics and their peripheral blood concentrations. DATA SOURCES: MEDLINE and Embase were searched using the following keywords: (positron emission tomography OR PET OR single-photon emission computed tomography OR SPECT) AND (dopamine OR D2) AND (receptor* OR occupanc*) AND antipsychotic*, with a limitation of English language (last search: December 14, 2019). STUDY SELECTION: The search identified 18 studies that met the following criteria: (1) including patients with schizophrenia spectrum disorders and/or healthy subjects, (2) using positron emission tomography or single-photon emission computed tomography, and (3) examining the time courses of D₂ occupancy with antipsychotics and their blood concentrations. DATA EXTRACTION: The ratios of D₂ occupancy reduction rate (%) from peak to blood concentration reduction rate (%) from peak (relative attenuation ratio) were calculated. RESULTS: Among the studies, oral risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, perospirone, haloperidol, sulpiride, and clozapine and long-acting injectable risperidone and haloperidol were included. Relative attenuation ratios were less than 1, indicating a slower central versus peripheral attenuation, across the time points for all antipsychotic types and doses with only a few exceptions. The ratio decreased in a dose-dependent as well as a peak D₂ occupancy-dependent fashion. It contrarily increased in a time-dependent manner. CONCLUSIONS: The findings indicate pharmacokinetic attenuation of antipsychotics was generally slower at the central versus the peripheral level and pose a critical challenge to the current dosing strategy that primarily relies on peripheral pharmacokinetics of antipsychotics.
AB - OBJECTIVE: The objective of this study was to examine the extent of possible dissociation in pharmacokinetic decay between central dopamine D₂ receptor occupancy with antipsychotics and their peripheral blood concentrations. DATA SOURCES: MEDLINE and Embase were searched using the following keywords: (positron emission tomography OR PET OR single-photon emission computed tomography OR SPECT) AND (dopamine OR D2) AND (receptor* OR occupanc*) AND antipsychotic*, with a limitation of English language (last search: December 14, 2019). STUDY SELECTION: The search identified 18 studies that met the following criteria: (1) including patients with schizophrenia spectrum disorders and/or healthy subjects, (2) using positron emission tomography or single-photon emission computed tomography, and (3) examining the time courses of D₂ occupancy with antipsychotics and their blood concentrations. DATA EXTRACTION: The ratios of D₂ occupancy reduction rate (%) from peak to blood concentration reduction rate (%) from peak (relative attenuation ratio) were calculated. RESULTS: Among the studies, oral risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, perospirone, haloperidol, sulpiride, and clozapine and long-acting injectable risperidone and haloperidol were included. Relative attenuation ratios were less than 1, indicating a slower central versus peripheral attenuation, across the time points for all antipsychotic types and doses with only a few exceptions. The ratio decreased in a dose-dependent as well as a peak D₂ occupancy-dependent fashion. It contrarily increased in a time-dependent manner. CONCLUSIONS: The findings indicate pharmacokinetic attenuation of antipsychotics was generally slower at the central versus the peripheral level and pose a critical challenge to the current dosing strategy that primarily relies on peripheral pharmacokinetics of antipsychotics.
UR - http://www.scopus.com/inward/record.url?scp=85088879747&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85088879747&partnerID=8YFLogxK
U2 - 10.4088/JCP.19r13113
DO - 10.4088/JCP.19r13113
M3 - Article
C2 - 32726002
AN - SCOPUS:85088879747
VL - 81
JO - Journal of Clinical Psychiatry
JF - Journal of Clinical Psychiatry
SN - 0160-6689
IS - 5
ER -